Modulation of serotonin and adenosine 2A receptors on intermittent hypoxia-induced respiratory recovery following mid-cervical contusion in the rat.

Abstract

The present study was designed to evaluate the therapeutic effectiveness and mechanism of acute intermittent hypoxia on respiratory function at distinct injured stages following mid-cervical spinal contusion. In the first experiment, adult male rats were received laminectomy or unilateral contusion at 3rd-4th cervical spinal cord at 9 weeks of age. The ventilatory behavior in response to mild acute intermittent hypercapnic-hypoxia [10 episodes of 5 minutes of hypoxia (10 % O2, 4 % CO2, 86 % N2) with 5 minutes of normoxia intervals] was measured by whole-body plethysmography at the acute (~3 days), subchronic (~2 weeks), and chronic (~8 weeks) injured stages. The minute ventilation of contused animals is significantly enhanced following acute intermittent hypercapnic-hypoxia due to an augmentation of the tidal volume at all-time points post-injury. However, acute intermittent hypercapnia-hypoxia induced ventilatory long-term facilitation was only observed in uninjured animals at the acute stage. During the second experiment, the effect of acute intermittent hypercapnic-hypoxia on respiration was examined in contused animals after a blockade of serotonin receptors, or adenosine 2A receptors. The results demonstrated that acute intermittent hypercapnic-hypoxia induced enhancement of minute ventilation was attenuated by a serotonin receptor antagonist (methysergide) but enhanced by an adenosine 2A receptor antagonist (KW6002) at the subchronic and chronic injured stages. These results suggested that acute intermittent hypercapnic-hypoxia can induce respiratory recovery from acute to chronic injured stages. The therapeutic effectiveness of intermittent hypercapnic-hypoxia is dampened by the inhibition of serotonin receptors, but a blockade of adenosine 2A receptors enhanced respiratory recovery induced by intermittent hypercapnic-hypoxia.